Primary alcohols hydrochloride

Aromatic primary amines differ markedly from aliphatic amines in their reaction with nitrous acid. Thus a cold aqueous solution of mono thylamine hydrochloride reacts with nitrous acid to give mainly the corresponding primary alcohol ... 

The oxidation of primary alcohols to aldehydes also suffers from the problem of overoxidation of the aldehyde to a carboxylic acid. Mild methods capable of stopping die oxidation at the aldehyde oxidation level are required if aldehydes are to be obtained. The most common and effective reagent for this purpose is pyridinium chlorochromate (PCC), produced by the reaction of pyridinium hydrochloride with chromium trioxide. This reagent is soluble in dichloromethane and smoothly oxidizes primary alcohols to aldehydes in high yields. Because of die mild, neutral reaction conditions and the use of stoichiomettic amounts of oxidant, the aldehyde product is not oxidized further. 

In the second route to l,20 acid chloride 23, prepared by treatment of 5-chlorothiophene-2-carboxylic acid 28 with SOCl2 is coupled with (5)-3-amino-1,2-propanediol hydrochloride 29 in the presence of NaHCCh to furnish the dihydroxy amide 30 (Scheme 3). The primary alcohol in 30 is then brominated by a solution of HBr in HOAc to produce the bromohydrin 31, which is then condensed with the morpholinoaniline derivative 18 to yield 32. Finally, the ring closure with N,N -carbonyldiimidazole (CDI) afforded 1. 

Barton devised a new method for the oxidation of primary alcohols to aldehydes involving in the first step conversion to the alkyl chloroformate (1) by adding a solution of the alcohol in ether to ether saturated with phosgene (15-20% w./v.) the solvent is removed at reduced pressure. If the alcohol is hindered, quinoline is added as catalyst and the quinoline hydrochloride removed by filtration. The next step, reaction with dimethyl sulfoxide, is attended with evolution of carbon... 

Other reactions. Blickenstalf and Chang found that the tosylates of primary alcohols are readily converted into the corresponding chlorides by reaction with pyridine hydrochloride in solution in dimethylformamide at room temperature. 

Oxidative animation. A different reaction pathway is adopted in the reaction of primary alcohols with hydroxylamine hydrochloride under the influence of [Cp IrCl2]2-Dehydrogenation of the alcohols (to form RCHO) and oximahon are fohowed by a rearrangement step, which leads to RCONH2-... 

The propionate derivative of oxazolidinone 214 was allowed to condensate with the aldehyde 215 to furnish 216 in 87% yield. Borohydride reduction of 216 gave diol 217. Selective tosylation of the primary alcohol resulted in spontaneous cyclization to give the pyrrolidinium tosylate salt, which was converted to its chloride salt 218 in 83% yield. Selective mono-deprotection of the salt afforded the free hydroxyl 219, which was acetylated and then subjected to hydrogenolysis in the presence IM hydrochloric acid to allow the isolation of the C(4)Me analogue 220 as its hydrochloride salt in quantitative yield. 

The major sales form of vitamin B6 is the hydrochlorid salt of the primary alcohol pyridoxine. Another vitamin B6 form introduced in the market is the dihydrochlo-rid salt of pyridoxamine. Both vitamin B6 forms are commercially produced via various straightforward chemical synthesis routes. The biologically active cofactor is the aldehyde pyridoxal-5 -phosphate, which is derived in human or animals from the vitamin B6 forms by oxidation or transamination before or after 5 phosphorylation by pyridoxal kinases. 

Preparation.—From Alcohols or other Halides. Factors affecting the formation of isomerically and optically pure alkyl halides from saturated aliphatic alcohols have been discussed by Hudson and co-workers. - Reactions with thionyl chloride give reduced amounts of rearrangement products if pyridine hydrochloride is added, and isomerically pure chlorides RCl from almost all alcohols ROH if HMPT or DMF is the solvent. In the latter medium (58) is a presumed intermediate, as is the case in the reaction of alcohols with Vilsmeier reagents (59, X = Cl or Br). Such species produce halides via inversion of configuration from secondary alcohols, presumably according to Scheme 24. In the related reaction of PCI3 with unhindered primary alcohols in DMF to produce alkyl... 

The modified procedure involves refluxing the N-substituted phthaUmide in alcohol with an equivalent quantity of hydrazine hydrate, followed by removal of the alcohol and heating the residue with hydrochloric acid on a steam bath the phthalyl hydtazide produced is filtered off, leaving the amine hydrochloride in solution. The Gabriel synthesis has been employed in the preparation of a wide variety of amino compounds, including aliphatic amines and amino acids it provides an unequivocal synthesis of a pure primary amine. 

Picolyl ethers are prepared from their chlorides by a Williamson ether synthesis (68-83% yield). Some selectivity for primary versus secondary alcohols can be achieved (ratios = 4.3-4.6 1). They are cleaved electrolytically ( — 1.4 V, 0.5 M HBF4, MeOH, 70% yield). Since picolyl chlorides are unstable as the free base, they must be generated from the hydrochloride prior to use. These derivatives are relatively stable to acid (CF3CO2H, HF/anisole). Cleavage can also be effected by hydrogenolysis in acetic acid. ... 

The Mannich reaction consists in the condensation of formaldehyde with ammonia or a primary or a secondary amine and a compound containing at least one hydrogen atom of pronounced reactivity the active hydrogen atom may be derived from a methylene group activated by a neighbouring keto group, or from a nitroparaffin, or it may be the o- or p-hydrogen atoms in phenols. Thus when acetophenone is boiled in alcoholic solution with formaldehyde and dimethylamine hydrochloride, the Mannich base P-dimethylamino-propiopbenone hydrochloride (I) is readily formed ... 

Experiments.—Being a primary hydrazide (of carbamic acid), semicarbazide reduces ammoniacal silver solutions and Fehling s solution. It reacts readily with aldehydes and ketones with the elimination of water and formation of semicarbazones, which, since they are more easily hydrolysed than are phenylhydrazones and oximes, are to be preferred to the latter for purposes of separation and purification of carbonyl compounds. Shake an aqueous solution of the hydrochloride (prepared as described above) with a few drops of benzaldehyde, isolate the semicarbazone and purify it by recrystallisation from alcohol. Melting point 214° decomp. Benzaldehyde semicarbazone is decomposed into its constituents by gentle warming with concentrated hydrochloric acid. 

Gerrard [11] had shown earlier that the slow addition of 0.5 mole of thionyl chloride to a mixture of pyridine (1.0 mole) and hydroxy compounds (n-butyl, M-amyl, or ethyl lactate—0.1 mole) gives pyridine hydrochloride and good yields of the sulfite (see Eq. 4). Primary and secondary alcohols with an aromatic nucleus in the a-position give chlorides in the absence of catalysts [12], For example, diphenylmethanol gives the chloride even at —78°C. Sulfites derived from tertiary alcohols are not known. The further addition of thionyl chloride converted the sulfite to the chlorosulfinate (see Eq. 5 and Table I). 

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